Arquette appeared in the Sega video game ESPN NFL 2K5, voicing himself as a "celebrity adversary" and manager of his own team, the Los Angeles Locos, as well as appearing as an unlockable character in Season Mode. He also appeared in the 2001 EA video game SSX Tricky, as the voice of lead character Eddie. He also starred in See Spot Run in 2001. Arquette starred in the 2007 ABC comedy series In Case of Emergency, which was canceled after one season. Since then, he has appeared in the 2008 film Hamlet 2, and reprised his role in Scream 4, again acting alongside Cox.[14] He appeared alongside his sister in the TV show Medium in January 2011.

He appeared in Rascal Flatts' music video for their song "Why Wait" in 2010. Arquette, a well-known horror fan, made his directorial debut with 2007's The Tripper, and has signed on to direct Glutton, a 3D psychological thriller. The film began shooting in July 2011 in Canada.[15] Arquette appeared on the 13th season of Dancing with the Stars, partnered with two time champion Kym Johnson. He was eliminated on November 1, 2011.

On October 7, 2013, Arquette's new show "Dream School" in which he plays a mentor to high-risk kids in LA, premiered on the Sundance Channel.[16]

During his time as champion, Arquette was mostly used as comic relief. He only appeared on two shows as champion, the May 1 Nitro and May 7 Slamboree pay-per-view. During the former, a vignette was shown, filmed on the set of Arquette's film 3000 Miles to Graceland, which also featured his wife Courteney Cox and their co-star Kurt Russell. In the vignette, Cox informs Russell that Arquette is the WCW World Heavyweight Champion, causing Russell to laugh and walk off and Arquette to chase after him with a steel chair. In another portion of the show, Arquette was seen backstage trembling in fear and attempting to "give back" the championship belt. He did, however, successfully defend the title against Tank Abbott with help from Page.[20]

Arquette held the title for 12 days until the Slamboree pay-per-view on May 7, 2000, when he was booked to defend the championship against Jarrett and Page in a Triple Cage match, the same match featured in the climax of Ready to Rumble. In the end, he turned on Page and gave the victory to Jarrett.[21] After Slamboree, Arquette cut a promo on the May 8 episode of Nitro, explaining that his entire friendship with Page and title run was a "swerve". Page subsequently ran down to the ring and hit him with a Diamond Cutter.[22] Arquette made one final appearance with WCW at the New Blood Rising pay-per-view on August 13, when he interfered in a match between Buff Bagwell and Kanyon.

Arquette was totally against becoming the WCW World Heavyweight Champion, believing that fans like himself would detest a non-wrestler winning the title. Vince Russo, who was the head booker for WCW at the time, insisted that Arquette becoming the champion would be good for the company and for publicity, and Arquette reluctantly agreed to the angle. All the money he made during his WCW tenure was donated to the families of Owen Hart (who died in a freak accident), Brian Pillman (who died from an undiagnosed heart condition), and Darren Drozdov (who became a quadriplegic after an in-ring accident).[23] After World Wrestling Federation/World Wrestling Entertainment (WWF/E) purchased WCW, Arquette's championship run was listed as the top reason for the "failure" of Nitro in a list published by WWE Magazine.[3]

On February 8, 2002, Arquette appeared on SmackDown!, popping up in the crowd with a sign that said "Former WCW World Champ".[24] On December 13, 2010, Arquette appeared on Raw as one of the presenters during the 2010 Slammy Awards. During that time, he adopted a comical villainouscharacter. He later teamed with Alex Riley in a handicap match in a losing effort against Randy Orton. Immediately following the match, Arquette and then WWE ChampionThe Miz tried to attack Orton, which led to Arquette being hit with a powerbomb through a table by Orton.[25] Arquette has also appeared in promotional commercials for the WWE's "Be A Star" anti-bullying campaign.

In May 2007, Image Comics (in conjunction with Raw Studios) published David Arquette's the Tripper, which was adapted for the comic book medium by artist Nat Jones and writer Joe Harris, with whom Arquette shared writing duties. Propr Collection is a clothing line run by Arquette and Ben Harper.[27] Arquette was briefly in a band by the name of Ear2000, who contributed a song to the Scream 2soundtrack and Scream 3soundtrack. The group, whose style blended hip-hop and rock, has since broken up. Arquette has also been a part of Washington's Red Museum, and recorded "Post Empire" with the band, which was released in 2011.[28]

Arquette is part owner of the Bootsy Bellows nightclub.[29] The club is named after Arquette's mother who was a burlesque dancer who danced under the name Bootsy Bellows.[30]

Arquette married actress Courteney Cox on June 12, 1999.[36] They have a daughter, Coco Riley Arquette, born June 13, 2004.[37][38]Jennifer Aniston is Coco's godmother.[39] On October 11, 2010, it was announced that Arquette and Cox were having a trial separation, but "still love each other deeply".[40] In June 2012, Arquette filed for divorce after nearly two years of separation from Cox.[41] The divorce became final in May 2013.[42]

Arquette checked into rehab for treatment of "alcohol and other issues" on January 1, 2011, shortly after celebrating New Year's Eve.[43] On April 8, 2011, Arquette announced on The Tonight Show with Jay Leno that he had reached the 100-day sober milestone. Later that year, Arquette confirmed on The Tonight Show that he had been sober for over nine months. In June 2012, while in Israel to film an episode of the travel show Trippin, Arquette belatedly celebrated his Bar Mitzvah at the Western Wall.[44] The presiding rabbi was Shmuel Rabinovitch.[45][46]

Arquette dated Entertainment Tonight correspondent Christina McLarty on/off from 2011. They announced they were expecting their first child together in November 2013.[47][48][49] McLarty gave birth to the couple's son Charlie West Arquette on April 28, 2014.[50] The couple announced their engagement in July, 2014.[51] They were married on April 12, 2015.[52]